SARS-CoV-2 in Pediatric Liver Transplant Recipients: The European Experience.

To the Editor: We read the article by Kehar et al (1) with great interest, in which the authors suggest that pediatric liver transplant (LT) recipients in North America were not at risk of worse outcomes compared to chronic liver disease patients (CLD). We hereby present our data from three international registries on coronavirus disease 2019 (COVID-19) in pediatric liver patients (CovidHep, SECURE-Liver, ERN RARE-LIVER), which offer a different viewpoint.

Twenty-one LT recipients and 16 CLD pediatric patients from 10 European centres developed confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (Table 1). LT recipients were more frequently hospitalized (38% vs 19%; relative risk [RR] 2.03; 95% confidence interval [CI] 0.7–6.4; P = 0.20) and presented more complications (19%) in comparison to CLD (0%). Two LT children required intensive care, one requiring non-invasive ventilation. There were no deaths. Inpatient LT recipients were more frequently on combined immunosuppression, specifically prednisone and mycophenolate mofetil (MMF) compared to outpatients (87.5% vs 7.7%; RR 0.09; 95% CI 0.02–0.41; P = 0.0003). Unlike what has been reported in adults, time since LT was probably not a factor, given that follow up spanned 1–8 years.

TABLE 1

Patient characteristics and clinical parameters of pediatric liver transplant recipients and patients non-transplanted with chronic liver disease with SARS-CoV-2 infection

	Liver transplant recipients (LT)	Non-transplanted, chronic liver disease patients (CLD)
n	21	16
Female	12 (57%)	7 (44%)
Median age (interquartile range)	10 (6–14)	12 (1–15)
Liver cirrhosis	4 (19%)	8 (50%)
Median years from transplantation (interquartile range)	4 (1–8)	n.a.
Liver disease aetiology
Biliary atresia	9 (43%)	3 (19%)
Autoimmune hepatitis	1 (5%)	4 (25%)
Alagille syndrome	2 (10%)	2 (13%)
Progressive familial intrahepatic cholestasis	3 (14%)	1 (6%)
Other entities∗	5 (24%)	6 (38%)
Comorbidities
Overweight (BMI > 25)	0	2 (13%)
Arterial hypertension	2 (10%)	1 (6%)
Pulmonary disease	1 (5%)	2 (13%)
Chronic kidney disease	2 (10%)	1 (6%)
Other chronic diseases	5 (24%)	5 (31%)
Symptoms of SARS-CoV-2 infection
Fever	8 (38%)	4 (25%)
Coughing	8 (38%)	5 (31%)
Shortness of breath	3 (14%)	3 (19%)
Fatigue	4 (19%)	0
Myalgia	0	1 (6%)
Outcome
Severe complications (exacerbation of chronic diarrhea, melena and hematochezia†, hemodialysis)	3 (14%)	0
Multisystem inflammatory syndrome (MISC) with bacterial superinfection	1 (5%)	0
Inpatient care	8 (38%)	3 (19%)
Intensive care (ICU admission)	2 (10%)	0
Non-invasive ventilation	1 (5%)	0
Invasive ventilation	0	0
Death	0	0
Immunosuppressive regimen of non-hospitalized patients
Tacrolimus mono	11 (52%)
Ciclosporin mono	1 (5%)
Tacrolimus + ciclosporin	1 (5%)
Prednisolone mono		2 (13%)
Azathioprine mono		1 (6%)
Adalimumab mono		1 (6%)
Prednisolone + azathioprine		3 (19%)
None		6 (38%)
Immunosuppressive regimen of hospitalized patients
Tacrolimus mono	2 (10%)
Tacrolimus + prednisolone	2 (10%)
Tacrolimus + mycophenolate mofetil	1 (5%)
Mycophenolate mofetil + prednisolone	1 (5%)
Ciclosporin + prednisolone	1 (5%)
Ciclosporin + mycophenolate mofetil + prednisolone	1 (5%)
None		3 (19%)

BMI = body mass index; CLD = chronic liver disease patients; ICU = intensive care unit; LT = liver transplant recipients; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2.

LT recipients: glycogen storage disease, methylmalonic aciduria, acute liver failure, neonatal sclerosing cholangitis, cholestasis and malnutrition, hepatoblastoma; CLD: IgG4-associated disease, PSC, Joubert syndrome, biliary cirrhosis, neonatal cholestasis, ARPKD.

Due to underlying liver disease.

The relative contributions of immunosuppression, comorbidity, age and other variables to host vulnerability to SARS-CoV2 infection remain unclear. It is possible that combined immunosuppression led to increased hospitalization of LT recipients. MMF discontinuation has recently been recommended to curb the risk of lymphopenia (2). Although this is a small cohort, we suggest that pediatric LT recipients under combined immunosuppression, especially using MMF, should be monitored carefully in case of SARS-CoV-2 infection and prioritized for vaccine studies.